Validation and accountability are vital in most scientific industries and especially so in the pharmaceutical and biotechnological industries. A major challenge to these industries is the need to demonstrate accurately and reproducibly that sterility is achieved and maintained throughout production lines within a plant. This must be done in a manner which meets the stringent requirements of regulatory bodies such as the United States FDA. Acceptable standards can be difficult to be met when a substance is transferred from one sterile location to another sterile location by non direct means.
One current practice includes providing a holding vessel into which substance can be transferred by means of a connecting valve. The holding vessel is transferred to the second sterile location and the substance is then transferred from the holding vessel into the second sterile location via one or more connecting valves. The connecting valves and holding vessel can be sterilised using conventional techniques such as gas, radiation or steam sterilisation. However during connection of the connecting valve to the first sterile location, the external connecting surface of the connecting valve is exposed to the atmosphere and sterility of the valve is compromised.
Alternative methods of substance transfer suffer from similar problems.
For example, in the use of an autoclavable port, where a non-sterile male port is attached to an empty non-sterile bulk vessel prior to sterilization, the entire assembled apparatus is then sterilised by autoclaving. However, a major disadvantage of this technique is that the vessel must be empty before sterilisation.
Alternatively, an irradiated port can be used, where a non-sterile male port is attached to an empty non-sterile disposable bag prior to sterilisation of the whole by irradiation. Again a major disadvantage associated with this system is that the bag must be empty before sterilisation.
A further method of substance transfer involves connecting a transfer port to a vessel under aseptic conditions. With this method it is irrelevant whether or not the vessel is empty or filled. However despite the necessity to undertake these actions in a designated ‘Grade A’ zone, there is an increased risk of contamination due to the making and breaking of various connections. The mere fact that a ‘Grade A’ zone is required to complete these actions requires a significant financial investment by a company wishing to employ this technique.
Another technique incorporates the use of a tube fuser. A sterile bulk vessel is attached to tubing emanating from a sterile port through a tube fuser. This technique is undesirable for numerous reasons including the restricted choice of tubing. This in turn limits the types of substance that can be transferred through the tubing. It is also undesirable to use wetted tubing. Furthermore there is also a potential risk of cross-contamination and re-contamination.
Despite the numerous attempts to find a sterile method of substance transfer none have been wholly successful. In all of the above techniques the sterility of the port or valve used to transfer the substance from one vessel to another is compromised during the connection process or is susceptible to contamination. This is undesirable and leads to problems when validating a product.
Piston-operated valves for the above applications are known. These act by moving a piston up and down or sliding over and back within an apertured housing so as to cover or uncover the fluid communication apertures of the housing. O-ring seals are provided for sealing between the open and closed valve positions. Such valves therefore have slots for receiving the O-rings and the difficulties of assuring that these slots and the spaces about them are not subject to contamination render them questionable for use in sterile transfer systems.
GB 1,573,482 discloses a rigid tubular member positioned within a flexible tube with one end of the tubular member being blocked by an integrally formed plug. A rigid shaft extends from the plug along the flexible tube and an area of weakness is defined between the plug and the tubular member. The plug is broken free from the tubular member by manually gripping the flexible tube from outside and pulling, bending or twisting the rigid shaft thus breaking it off the tubular member and opening the tubular member for fluid transfer. The opened end can be closed again by sealingly re-inserting the plug into it.
AT 006,052 U1 describes a valve having a hollow housing with two open ends and a piston movable within the housing. A deformable O-ring is disposed around an end portion of the piston which blocks one of the open ends of the housing, the O-ring providing a seal between the end portion of the piston and the opening. The piston is connected to the housing via a screw thread so that rotation of the housing about the piston causes the piston to move away from the opening to open the valve. Reverse rotation of the housing re-closes the valve.
WO 03/090,842 provides a piston-operated valve having an elongate open-ended housing in which one of the ends is blocked with a “tear-away” seal formed continuously with the housing. On operation of an actuator, the piston moves within the housing and breaks the seal thus opening the valve for passage of fluid. The broken-away seal is retained in a deployed position away from the open end of the valve. This valve cannot be re-closed after the seal has been broken and therefore there exists a risk of contamination of the environment from e.g. biological material being transferred through the valve.